text: Researchers used multi-disciplinary approach to design NNRTIs with better resistance profile and an increased genetic barrier to the development of resistance.  A new class of compounds, diarylpyrimide (DAPY), were discovered with the replacement of the central triazine ring from the DATA compounds, with a pyrimidine. This new class was more effective against drug resistant HIV-1 strains than the corresponding DATA analogs. The replacement enabled substitutions to the CH-group at the 5-position of the central aromatic ring. One of the first DAPY compounds, dapivirine (with R= 2,4,6-trimethylanilino, R = R = H and Y = NH) was found to be effective against drug-resistant HIV-1 strains. Systematic chemical substitutions were made at the R, R, R and Y positions to find new DAPY derivatives. This led to the discovery of etravirine which has a bromine substitution at the 5-position (R) of the pyrimidine ring (with R = 2,6-dimethyl-4-cyanoanilino, R = NH and Y = O) (figure 5). Etravirine was discovered by researchers at the Jansen Research Foundation and Tibotec and approved in 2008 by the FDA. It is used in treatment-experienced adult patients with HIV infection that is multidrug resistant in combination with other antiretroviral drugs.